As reported in the literature, a number of routes are known for the synthesis of alpha-amino acids. The best-known route is the Strecker synthesis route (see, Introduction to Organic Chemistry, Streitwieser and Heathcock, Macmillan Publishing Co., Inc. New York, 1981). In this method a suitable aldehyde is treated with ammonia and HCN, so that an alpha-amino nitrile is formed, which is subsequently subjected to a hydrolysis reaction to provide the corresponding alpha-amino acid.
Also, it has been shown (see, Ugi, I. Angew. Chem., Intl. Ed. Engl., 1982, Vol. 21, pp. 810-819, and Ugi, I. et al., J. Prokt. Chem., 1997, Vol. 339, p. 499) that the reaction of an isocyanide (X1NC) with a carboxylic acid (X2COOH), an aldehyde (X3CHO) and an amine (X4NH2) under the appropriate conditions provided the corresponding dipeptide (N-alkyl-N-acyl-alpha amino amide) as follows:X1—NC+X2—COOH+X3—CHO+X4NH2→X2—CO—NX4—CHX3—CO—NX1H                N-alkyl-N-acyl-alpha amino amide (i.e., a dipeptide)        
In an attempt to convert the dipeptides to their corresponding alpha-amino acids, Ugi used chiral ferrocenylamine in the above-mentioned reaction. The desired amino acids were obtained with low to modest diastereoselectiveity. (See, Ugi I. et al., Tetrahedron Lett., 1986, Vol. 42, pp. 5931-5940).
Furthermore, the use of a convertible isocyanide in the Ugi reaction, namely cyclohexene-isocyanide, followed by hydrolysis to provide the corresponding peptide carboxylic acid, has been demonstrated (see, Armstrong, R. W. et al., J. Am. Chem. Soc., 1996, Vol. 118, p. 2574) as follows:                 N-alkyl-N-acyl-alpha amino acid (i.e., a peptide carboxylic acid)        
In addition, the use of phenyl-isocyanide and pyridyl-isocyanide was demonstrated in the conversion of dipeptides made by Ugi into pyrrole derivatives (see, Mjalii, et al., Tet. Lett., 1996, Vol.37, pp.2943-2946).
Moreover, the use of sugar derivatives (protected galactososylamine and arabinopyranosylamine) as chiral amines with t-butyl-isocyanide converted the dipeptides made by Ugi into the corresponding sugar dipeptides, which were then converted in four chemical steps:
(1) HCl, MeOH, 0° C. to RT, 4 h;
(2) H2O, 12 h, RT;
(3) 6N HCl, 80° C., 24 h; and
(4) Amberlite, IR 200
using very harsh conditions to the corresponding alpha-amino acids as shown below:X2—CO—N(sugar)-CHX3—CO—NH—C(CH3)3→NH3Cl—CHX3—COOHwhere used was an aldehyde, X3CHO, where X3=Ph, t-Bu, (CH2)3 COOH, Bn, or para-Cl-Ph (see, Kunz, H. et al., Tet. Lett., 1988, Vol. 29, p. 5487, and Kunz, H. et al., Tet. Lett., 1989, Vol. 30, pp. 4109-4110).
This sugar amine was also described being made by utilizing different isocyanides and then being converted in three chemical steps:
(1) HCl, MeOH, 0° C. to RT, 4 h;
(2) H2O, 12 h, RT; and
(3) 2N HCl, 60° C., 24 has shown below: where used was an aldehyde, X3CHO, where X3=Ph, t-Bu, (CH2)4COOH, Bn, or H2CF═CH (see, Linderman, R. J., J. Am. Chem. Soc., 1999, Vol. 64, pp. 336-337).
Also, it has been reported (see, Ugi et al., Angew. Chem. Intl. Ed. Engl., 1996, Vol. 35, p.173) that the reaction of unprotected alpha-amino acids (namely valine, phenyl alanine and proline) with a series of isocyanides and aldehydes in MeOH provided the corresponding three amino peptides with excellent yield and good diastereoselectivity as shown below:X4—NC+NH2—CXH—COOH+X3—CHO→X4—NH—CO—CHX3—NH—CHX—COOMe                N-alkyl-N-acyl-alpha amino amideMore specifically, the synthesis of the following three compounds has been reported by this method:         